Effects of classical olfactory training in patients with COVID-19-related persistent loss of smell.

PURPOSE: The management of post-COVID-19 persistent olfactory dysfunction (OD) is uncertain. Currently, olfactory training is the only evidence-based therapy for post-viral OD. In this study, we evaluated the effectiveness of classical olfactory training (COT) in the treatment of post-COVID-19 persistent OD. MATERIALS AND METHODS: Patients with persistent OD after COVID-19 were assessed using the Sniffin' Sticks test. Fifty-one patients were then divided into two groups based on personal preference: the COT group (n = 31) included subjects who performed COT over 12 weeks, and the control group (n = 20) included subjects who did not receive any treatment. After the exclusion of eight patients, the olfactory performances of 43 patients were re-evaluated and compared to the baseline values. RESULTS: A significantly higher proportion of patients in the COT group improved their olfactory scores above the clinically important difference compared to the control group (40% versus 6%) (p = 0.014). The subjective smell improvement by COT was independent of age, gender, OD duration, presence of parosmia, or the initial olfactory score (all p > 0.05). CONCLUSION: Twelve weeks of COT appears to increase the olfactory sensitivity in patients with persistent OD following COVID-19.

Changes in antimicrobial resistance and outcomes of health care-associated infections.

To describe the change in the epidemiology of health care-associated infections (HAI), resistance and predictors of fatality we conducted a nationwide study in 24 hospitals between 2015 and 2018. The 30-day fatality rate was 22% in 2015 and increased to 25% in 2018. In BSI, a significant increasing trend was observed for Candida and Enterococcus. The highest rate of 30-day fatality was detected among the patients with pneumonia (32%). In pneumonia, Pseudomonas infections increased in 2018. Colistin resistance increased and significantly associated with 30-day fatality in Pseudomonas infections. Among S. aureus methicillin, resistance increased from 31 to 41%.

Mortality predictors of Staphylococcus aureus bacteremia: a prospective multicenter study.

BACKGROUND: Staphylococcus aureus is one of the causes of both community and healthcare-associated bacteremia. The attributable mortality of S. aureus bacteremia (SAB) is still higher and predictors for mortality and clinical outcomes of this condition are need to be clarified. In this prospective observational study, we aimed to examine the predictive factors for mortality in patients with SAB in eight Turkish tertiary care hospitals. METHODS: Adult patients with signs and symptoms of bacteremia with positive blood cultures for S. aureus were included. All data for episodes of SAB including demographics, clinical and laboratory findings, antibiotics, and outcome were recorded for a 3-year (2010-2012) period. Cox proportional hazard model with forward selection was used to assess the independent effect of risk factors on mortality. A 28-day mortality was the dependent variable in the Cox regression analysis. RESULTS: A total of 255 episodes of SAB were enrolled. The median age of the patients was 59 years. Fifty-five percent of the episodes were considered as primary SAB and vascular catheter was the source of 42.1 %. Healthcare associated SAB was defined in 55.7 %. Blood cultures yielded methicillin-resistant S. aureus (MRSA) as a cause of SAB in 39.2 %. Initial empirical therapy was inappropriate in 28.2 %. Although overall mortality was observed in 52 (20.4 %), 28-day mortality rate was 15.3 %. Both the numbers of initial inappropriate empirical antibiotic treatment and the median hours to start an appropriate antibiotic between the cases of fatal outcome and survivors after fever onset were found to be similar (12/39 vs 60/216 and 6 vs 12 h, respectively; p > 0.05). High Charlson comorbidity index (CCI) score (p = 0.002), MRSA (p = 0.017), intensive care unit (ICU) admission (p < 0.001) and prior exposure to antibiotics (p = 0.002) all were significantly associated with mortality. The Cox analysis defined age [Hazard Ratio (HR) 1.03; p = 0.023], ICU admission (HR 6.9; p = 0.002), and high CCI score (HR 1.32; p = 0.002) as the independent predictive factors mortality. CONCLUSIONS: The results of this prospective study showed that age, ICU stay and high CCI score of a patient were the independent predictors of mortality and MRSA was also significantly associated with mortality in SAB.

Comparative Transcriptomic Analyses of Peripheral Blood Mononuclear Cells of COVID-19 Patients without Pneumonia and with Severe Pneumonia in the First Year of Follow-Up.

The multisystemic effects of COVID-19 may continue for a longer time period following the acute phase, depending on the severity of the disease. However, long-term systemic transcriptomic changes associated with COVID-19 disease and the impact of disease severity are not fully understood. We aimed to investigate the impact of COVID-19 and its severity on transcriptomic alterations in peripheral blood mononuclear cells (PBMCs) following 1 year of the disease. PBMCs were isolated from the peripheral blood of healthy control donors who did not have COVID-19 (C; n = 13), from COVID-19 patients without pneumonia (NP; n = 11), and from COVID-19 patients with severe pneumonia (SP; n = 10) after 1-year of follow-up. Following RNA isolation from PBMCs, high-quality RNAs were sequenced after creating a library. Differentially expressed genes (DEGs) and differentially expressed long non-coding RNAs (DElncRNAs) were identified using Benjamini-Hochberg correction and they were analysed for hierarchical clustering and principal component analysis (PCA). Intergroup comparisons (C vs. NP, C vs. SP, and NP vs. SP) of DEGs and DElncRNAs were performed and hub genes were determined. Functional enrichment analyses of DEGs and DElncRNAs were made using Metascape (v3.5.20240101) and the first version of NCPATH. The RNA sequencing analysis revealed 4843 DEGs and 1056 DElncRNAs in "C vs. NP", 1651 DEGs and 577 DElncRNAs in "C vs. SP", and 954 DEGs and 148 DElncRNAs in "NP vs. SP", with 291 DEGs and 70 DElncRNAs shared across all groups, respectively. We identified 14 hub genes from 291 DEGs, with functional enrichment analysis showing upregulated DEGs mainly linked to inflammation and osteoclast differentiation and downregulated DEGs to viral infections and immune responses. The analysis showed that 291 common and 14 hub genes were associated with pneumonia and that these genes could be regulated by the transcription factors JUN and NFκB1 carrying the NFκB binding site. We also revealed unique immune cell signatures across DEG categories indicating that the upregulated DEGs were associated with neutrophils and monocytes, while downregulated DEGs were associated with CD4 memory effector T cells. The comparative transcriptomic analysis of NP and SP groups with 52 gene signatures suggestive of IPF risk showed a lower risk of IPF in the SP group than the NP patients. Our findings suggest that COVID-19 may cause long term pathologies by modulating the expression of various DEGs, DeLncRNAs, and hub genes at the cellular level.

Evaluation of the implementation of WHO infection prevention and control core components in Turkish health care facilities: results from a WHO infection prevention and control assessment framework (IPCAF)-based survey.

BACKGROUND: The core components (CCs) of infection prevention and control (IPC) from World Health Organization (WHO) are crucial for the safety and quality of health care. Our objective was to examine the level of implementation of WHO infection prevention and control core components (IPC CC) in a developing country. We also aimed to evaluate health care-associated infections (HAIs) and antimicrobial resistance (AMR) in intensive care units (ICUs) in association with implemented IPC CCs. METHODS: Members of the Turkish Infectious Diseases and Clinical Microbiology Specialization Association (EKMUD) were invited to the study via e-mail. Volunteer members of any healt care facilities (HCFs) participated in the study. The investigating doctor of each HCF filled out a questionnaire to collect data on IPC implementations, including the Infection Prevention and Control Assessment Framework (IPCAF) and HAIs/AMR in ICUs in 2021. RESULTS: A total of 68 HCFs from seven regions in Türkiye and the Turkish Republic of Northern Cyprus participated while 85% of these were tertiary care hospitals. Fifty (73.5%) HCFs had advanced IPC level, whereas 16 (23.5%) of the 68 hospitals had intermediate IPC levels. The hospitals' median (IQR) IPCAF score was 668.8 (125.0) points. Workload, staffing and occupancy (CC7; median 70 points) and multimodal strategies (CC5; median 75 points) had the lowest scores. The limited number of nurses were the most important problems. Hospitals with a bed capacity of > 1000 beds had higher rates of HAIs. Certified IPC specialists, frequent feedback, and enough nurses reduced HAIs. The most common HAIs were central line-associated blood stream infections. Most HAIs were caused by gram negative bacteria, which have a high AMR. CONCLUSIONS: Most HCFs had an advanced level of IPC implementation, for which staffing was an important driver. To further improve care quality and ensure everyone has access to safe care, it is a key element to have enough staff, the availability of certified IPC specialists, and frequent feedback. Although there is a significant decrease in HAI rates compared to previous years, HAI rates are still high and AMR is an important problem. Increasing nurses and reducing workload can prevent HAIs and AMR. Nationwide "Antibiotic Stewardship Programme" should be initiated.

The association of antiviral drugs with COVID-19 morbidity: The retrospective analysis of a nationwide COVID-19 cohort.

Background and objectives: Although several repurposed antiviral drugs have been used for the treatment of COVID-19, only a few such as remdesivir and molnupiravir have shown promising effects. The objectives of our study were to investigate the association of repurposed antiviral drugs with COVID-19 morbidity. Methods: Patients admitted to 26 different hospitals located in 16 different provinces between March 11-July 18, 2020, were enrolled. Case definition was based on WHO criteria. Patients were managed according to the guidelines by Scientific Board of Ministry of Health of Turkey. Primary outcomes were length of hospitalization, intensive care unit (ICU) requirement, and intubation. Results: We retrospectively evaluated 1,472 COVID-19 adult patients; 57.1% were men (mean age = 51.9 ± 17.7years). A total of 210 (14.3%) had severe pneumonia, 115 (7.8%) were admitted to ICUs, and 69 (4.7%) were intubated during hospitalization. The median (interquartile range) of duration of hospitalization, including ICU admission, was 7 (5-12) days. Favipiravir (n = 328), lopinavir/ritonavir (n = 55), and oseltamivir (n = 761) were administered as antiviral agents, and hydroxychloroquine (HCQ, n = 1,382) and azithromycin (n = 738) were used for their immunomodulatory activity. Lopinavir/ritonavir (ß [95% CI]: 4.71 [2.31-7.11]; p = 0.001), favipiravir (ß [95% CI]: 3.55 [2.56-4.55]; p = 0.001) and HCQ (ß [95% CI]: 0.84 [0.02-1.67]; p = 0.046) were associated with increased risk of lengthy hospital stays. Furthermore, favipiravir was associated with increased risks of ICU admission (OR [95% CI]: 3.02 [1.70-5.35]; p = 0.001) and invasive mechanical ventilation requirement (OR [95% CI]: 2.94 [1.28-6.75]; p = 0.011). Conclusion: Our findings demonstrated that antiviral drugs including lopinavir, ritonavir, and favipiravir were associated with negative clinical outcomes such as increased risks for lengthy hospital stay, ICU admission, and invasive mechanical ventilation requirement. Therefore, repurposing such agents without proven clinical evidence might not be the best approach for COVID-19 treatment.

Comparison of an inactivated Covid19 vaccine-induced antibody response with concurrent natural Covid19 infection.

OBJECTIVES: The risk of contracting SARS-CoV-2 is high among the health care workers (HCW). The comparison between the antibody response to an inactivated Covid19 vaccine and the antibodies that developed during Covid-19 infection has not been elucidated. In this study, vaccine-induced antibody levels were compared with the antibodies developed in naturally infected HCWs. METHODS: Eighty vaccinated individuals and 80 Covid-19 patients enrolled to the study. Both groups were matched on age, gender and antibody testing time. Anti-SARS-CoV-2 total Ig (Roche) and Anti-SARS-CoV-2 ELISA (IgG) (Euroimmun, Germany) were used to detect antibodies. RESULTS: The anti-S positivity were determined to be 96.2% and 92.5% in vaccinated and patient groups (p=0.303) while the anti-N positivity was 51.2% and 98.8%, respectively (p=<0,0001). The median values for anti-S and anti-N antibodies were statistically significant between both groups. When the vaccinated group was compared with the severe and non-severe patient groups, statistically significant differences were found for both regarding anti-S1 and anti-N antibody titers (p=0,012, p=<0,0001, respectively). For the patient group, there was a positive correlation between the age and anti-S1 antibody titers (r=0.333; p=0.003) and there was also a statistically significant increase in anti-N antibody titers in time (r=0.505; p=0.0001). CONCLUSION: The anti-S seroconversion ratio in vaccinated individuals were higher than what was reported by the vaccine manufacturer. The antibody titers in the vaccinated group were lower than the patients group. The decrease in anti-S1 antibody titers in time were considered to be a disadvantage and an undesired phenomenon.

Awareness of influenza and pneumococcal vaccines in diabetic patients.

PURPOSE: In our study, it was aimed to evaluate the awareness of diabetic patients about vaccination status and vaccines. METHODS: This cross-sectional study was conducted between January 2019 and February 2019. A survey questioning the level of knowledge about and vaccination status for influenza and pneumonia vaccines was applied by face-to-face interviews with patients with diabetes mellitus who admitted to the diabetes outpatient clinic. All results were evaluated with SPSS-20.0. RESULTS: A total of 202 patients [66 male (32.7%) and 136 female (67.3%) patients; with a mean age of 57.7 ± 11.3 years and mean duration of diabetes 10.7 ± 7.9 years] were recruited in the study. Majority of the patients (92.6%) were type 2 DM patients. 59.4% of the patients had never been vaccinated. The rate of those who had pneumonia vaccine was very low, only 14.7%. The vast majority of the patients had knowledge about vaccines and their most common source of information was nurses. 53% of patients believed that diabetic patients should be vaccinated regularly. 16.8% of the patients were reluctant to have the recommended vaccine. The factor with greatest impact on this was that they did not consider the vaccine necessary. 52.5% of the patients recommended to be vaccinated had the recommended vaccine. 26.4% of the patients who were not enthusiastic about the recommended vaccine had pneumococcal vaccine after being informed about the vaccine. CONCLUSION: It was observed that the information given about vaccines positively affected the vaccination rate. The main barrier to vaccination was the lack of information about the need for influenza vaccination. Designing strategies and training programs for healthcare professionals and patients should be the main goal to improve vaccination coverage and vaccination rates.

The predictors of COVID-19 mortality in a nationwide cohort of Turkish patients.

The COVID-19-related death rate varies between countries and is affected by various risk factors. This multicenter registry study was designed to evaluate the mortality rate and the related risk factors in Turkey. We retrospectively evaluated 1500 adults with COVID-19 from 26 centers who were hospitalized between March 11 and July 31, 2020. In the study group, 1041 and 459 cases were diagnosed as definite and highly probable cases, respectively. There were 993 PCR-positive cases (66.2%). Among all cases, 1144 (76.3%) were diagnosed with non-severe pneumonia, whereas 212 (14.1%) had severe pneumonia. Death occurred in 67 patients, corresponding to a mortality rate of 4.5% (95% CI:3.5-5.6). The univariate analysis demonstrated that various factors, including male sex, age ≥65 years and the presence of dyspnea or confusion, malignity, chronic obstructive lung disease, interstitial lung disease, immunosuppressive conditions, severe pneumonia, multiorgan dysfunction, and sepsis, were positively associated with mortality. Favipiravir, hydroxychloroquine and azithromycin were not associated with survival. Following multivariate analysis, male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were found to be independent risk factors for mortality. Among the biomarkers, procalcitonin levels on the 3rd-5th days of admission showed the strongest associations with mortality (OR: 6.18; 1.6-23.93). This study demonstrated that the mortality rate in hospitalized patients in the early phase of the COVID-19 pandemic was a serious threat and that those patients with male sex, severe pneumonia, multiorgan dysfunction, malignancy, sepsis and interstitial lung diseases were at increased risk of mortality; therefore, such patients should be closely monitored.

Surgical site infection rates in 16 cities in Turkey: findings of the International Nosocomial Infection Control Consortium (INICC).

BACKGROUND: Surgical site infections (SSIs) are a threat to patient safety; however, there were no available data on SSI rates stratified by surgical procedure (SP) in Turkey. METHODS: Between January 2005 and December 2011, a cohort prospective surveillance study on SSIs was conducted by the International Nosocomial Infection Control Consortium (INICC) in 20 hospitals in 16 Turkish cities. Data from hospitalized patients were registered using the Centers for Disease Control and Prevention (CDC) National Healthcare Safety Network (NHSN) methods and definitions for SSIs. Surgical procedures (SPs) were classified into 22 types according to International Classification of Diseases, Ninth Revision criteria. RESULTS: We recorded 1879 SSIs, associated with 41,563 SPs (4.3%; 95% confidence interval, 4.3-4.7). Among the results, the SSI rate per type of SP compared with rates reported by the INICC and CDC NHSN were 11.9% for ventricular shunt (vs 12.9% vs 5.6%); 5.3% for craniotomy (vs 4.4% vs 2.6%); 4.9% for coronary bypass with chest and donor incision (vs 4.5 vs 2.9); 3.5% for hip prosthesis (vs 2.6% vs 1.3%), and 3.0% for cesarean section (vs 0.7% vs 1.8%). CONCLUSIONS: In most of the 22 types of SP analyzed, our SSI rates were higher than the CDC NHSN rates and similar to the INICC rates. This study advances the knowledge of SSI epidemiology in Turkey, allowing the implementation of targeted interventions.

Withdrawal of Staphylococcus aureus from intensive care units in Turkey.

BACKGROUND: In the past, Staphylococcus aureus infections have displayed various patterns of epidemiologic curves in hospitals, particularly in intensive care units (ICUs). This study aimed to characterize the current trend in a nationwide survey of ICUs in Turkey. METHODS: A total of 88 ICUs from 36 Turkish tertiary hospitals were included in this retrospective study, which was performed during the first 3 months of both 2008 (period [P] 1) and 2011 (P2). A P value ≤.01 was considered significant. RESULTS: Although overall rates of hospital-acquired infection (HAI) and device-associated infection densities were similar in P1 and P2, the densities of HAIs due to S aureus and methicillin-resistant S aureus (MRSA) were significantly lower in P2 (P < .0001). However, the proportion of HAIs due to Acinetobacter was significantly higher in P2 (P < .0001). CONCLUSIONS: The incidence of S aureus infections is declining rapidly in Turkish ICUs, with potential impacts on empirical treatment strategies in these ICUs.